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Telomeric G-quadruplexes are a substrate and site of localization for human telomerase

Journal Article


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Abstract


  • It has been hypothesized that G-quadruplexes can sequester the 3′ end of the telomere and prevent it from being extended by telomerase. Here we purify and characterize stable, conformationally homogenous human telomeric G-quadruplexes, and demonstrate that human telomerase is able to extend parallel, intermolecular conformations in vitro. These G-quadruplexes align correctly with the RNA template of telomerase, demonstrating that at least partial G-quadruplex resolution is required. A highly purified preparation of human telomerase retains this extension ability, establishing that the core telomerase enzyme complex is sufficient for partial G-quadruplex resolution and extension. The parallel-specific G-quadruplex ligand N-methyl mesoporphyrin IX (NMM) causes an increase in telomeric G-quadruplexes, and we show that telomerase colocalizes with a subset of telomeric G-quadruplexes in vivo. The ability of telomerase to partially unwind, extend and localize to these structures implies that parallel telomeric G-quadruplexes may play an important biological role.

Authors


  •   Moye, Aaron L. (external author)
  •   Porter, Karina C. (external author)
  •   Cohen, Scott (external author)
  •   Phan, Tram (external author)
  •   Zyner, Katherine G. (external author)
  •   Sasaki, Natsuki (external author)
  •   Lovrecz, George (external author)
  •   Beck, Jennifer L.
  •   Bryan, Tracy (external author)

Publication Date


  • 2015

Citation


  • Moye, A. L., Porter, K. C., Cohen, S. B., Phan, T., Zyner, K. G., Sasaki, N., Lovrecz, G. O., Beck, J. L. & Bryan, T. M. (2015). Telomeric G-quadruplexes are a substrate and site of localization for human telomerase. Nature Communications, 6 (July), 7643-1-7643-12.

Scopus Eid


  • 2-s2.0-84937003373

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4254&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3231

Has Global Citation Frequency


Start Page


  • 7643-1

End Page


  • 7643-12

Volume


  • 6

Issue


  • July

Place Of Publication


  • United Kingdom

Abstract


  • It has been hypothesized that G-quadruplexes can sequester the 3′ end of the telomere and prevent it from being extended by telomerase. Here we purify and characterize stable, conformationally homogenous human telomeric G-quadruplexes, and demonstrate that human telomerase is able to extend parallel, intermolecular conformations in vitro. These G-quadruplexes align correctly with the RNA template of telomerase, demonstrating that at least partial G-quadruplex resolution is required. A highly purified preparation of human telomerase retains this extension ability, establishing that the core telomerase enzyme complex is sufficient for partial G-quadruplex resolution and extension. The parallel-specific G-quadruplex ligand N-methyl mesoporphyrin IX (NMM) causes an increase in telomeric G-quadruplexes, and we show that telomerase colocalizes with a subset of telomeric G-quadruplexes in vivo. The ability of telomerase to partially unwind, extend and localize to these structures implies that parallel telomeric G-quadruplexes may play an important biological role.

Authors


  •   Moye, Aaron L. (external author)
  •   Porter, Karina C. (external author)
  •   Cohen, Scott (external author)
  •   Phan, Tram (external author)
  •   Zyner, Katherine G. (external author)
  •   Sasaki, Natsuki (external author)
  •   Lovrecz, George (external author)
  •   Beck, Jennifer L.
  •   Bryan, Tracy (external author)

Publication Date


  • 2015

Citation


  • Moye, A. L., Porter, K. C., Cohen, S. B., Phan, T., Zyner, K. G., Sasaki, N., Lovrecz, G. O., Beck, J. L. & Bryan, T. M. (2015). Telomeric G-quadruplexes are a substrate and site of localization for human telomerase. Nature Communications, 6 (July), 7643-1-7643-12.

Scopus Eid


  • 2-s2.0-84937003373

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4254&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3231

Has Global Citation Frequency


Start Page


  • 7643-1

End Page


  • 7643-12

Volume


  • 6

Issue


  • July

Place Of Publication


  • United Kingdom